Project Summary/Abstract Over the past ten years, a new inhaled nicotine device, popularly referred to as an electronic cigarette (e-cig), has become increasingly popular around the world, particularly in the United States where more than 79% of US adults are currently aware of the devices and 3.7% are using one on a regular basis. Current e-cig use is most prevalent among current smokers (15.9%) and recent ex-smokers (22.0%) and is very uncommon among adult never cigarette smokers (0.4%). As the popularity of these devices has increased, the types of devices and the associated products available to users have diversified, making it difficult for users and non-users alike to understand the devices and their potential harms or benefits. E-cigarettes deliver high doses of fine particles and highly oxidizing free radicals in the human respiratory system. Fine particles are emitted when the solvents propylene glycol and vegetable glycerin, along with flavors, additives and nicotine are aerosolized, and respiratory and cardiovascular effects have been documented, but adequate assessments are lacking. The recent development of a Standardized Research E-Cig (SREC) with both medium (15 mg/ml) and placebo (zero mg/ml) nicotine concentration in the liquid now offers the possibility of testing the likely health effects of attempting to switch from cigarette smoking to an SREC and to examine the effects of nicotine in the liquid on that process. Our long term goal is to understand the likely health effects of cigarette smokers switching to a Standardized Research E-Cig (SREC) and to assess the role of nicotine delivery on switching, acceptability and markers of health outcomes. The specific objective of this proposal is to recruit a cohort of 240 current exclusive daily smokers and to measure a comprehensive battery of health markers at baseline and at 3 and 6 weeks after attempting to switch completely to SRECs containing either zero or 15 mg/ml nicotine in a randomized double-blind, placebo-controlled design. The NIH-funded Penn State Tobacco Center of Regulatory Science has conducted a number of preliminary studies of electronic cigarette use. These studies have provided us with the infrastructure and expertise to conduct a study of health risks associated with switching to a Standardized Research E-Cig, with the following three specific aims: AIM 1. To characterize the short-term effects of attempting to switch from traditional cigarette smoking to a Standardized Research E-Cig using a comprehensive battery of measures (e.g. carcinogen biomarker, NNAL, pulmonary function testing, lipid panel, glutathione, exhaled CO, blood nicotine and cotinine, BP etc.) over 6 weeks. AIM 2. To compare the effects of nicotine containing versus zero nicotine liquid on reduction of smoking behavior and health markers. AIM 3. At the end of each participant's 6 week participation they will be provided with information about the health effects of tobacco product use, how to purchase SREC supplies if they wish to continue using and sources of assistance to quit smoking, and they will be asked to complete telephone and online survey 4 weeks later.